The snake distal tubule responds to apical Na concentrations in a way that is unique when compared with observations in other Na-transporting epithelia. When the apical Na concentration is increased above 30 mM, the transepithelial voltage, transepithelial resistance RT, and short-circuit current I respond sharply consistent with stimulation of Na transport. Thereafter, transepithelial voltage and short-circuit current I increases. Since this apparent reduction (self-depression) of Na transport occurs in parallel with marked cell swelling, it is suggested that changes in the ionic composition of transporting cells are involved. The proposed work will test this hypothesis in experiments using isolated perfused distal tubules. In each distal tubule, transepithelial Na transport, volume transport, in parrellel with 1) epithelial cell volume changes and 2) initial, intermediary, and final cellular Na and K concentrations. These experiments will be conducted under control conditions and experimental conditions of 1) variable luminal Na concentrations, and 2) variable luminal membrane permeabilities. The experiments are designed to allow for the first time structure-function-composition correlations to be made in a Na-transporting epithelium that 1) consists of a single layer of epithelial cells alone and 2) displays inique structural and functional and presumably compositional responses to luminal Na concentrations. These studies are preceded by additional preliminary studies necessary for the successful completion of the proposed work.